Interferon mediated prophylactic protection against respiratory viruses conferred by a prototype live attenuated influenza virus vaccine lacking non-structural protein 1.
Interferon mediated prophylactic protection against respiratory viruses conferred by a prototype live attenuated influenza virus vaccine lacking non-structural protein 1.
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DOI：
10.1038/s41598-021-01780-8
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发表时间：
2021-11-12
影响因子：
4.6
通讯作者：
García-Sastre A
中科院分区：
文献类型：
--
作者：
Rathnasinghe R;Salvatore M;Zheng H;Jangra S;Kehrer T;Mena I;Schotsaert M;Muster T;Palese P;García-Sastre A
甲型流感非结构蛋白1 （NS1）因其在病毒感染期间阻碍I型干扰素（IFN）合成的能力而闻名。缺乏NS1的流感病毒（ΔNS1）正处于临床开发阶段，可作为人类流感病毒减毒活疫苗，并诱导强效流感病毒特异性体液和细胞适应性免疫反应。ΔNS1流感病毒的衰减是由于其高干扰素诱导特性，这限制了它们在体内的复制。该研究表明，ΔNS1病毒预处理可导致抗病毒状态，阻止同源和异源病毒的后续复制，从而预防包括SARS-CoV-2在内的病毒呼吸道病原体的疾病。我们的研究表明，ΔNS1流感病毒可用于预防流感、SARS-CoV-2和其他人类呼吸道病毒感染，并且基于ΔNS1减毒活病毒的流感病毒疫苗将从给药的那一刻起，首先通过非特异性先天免疫诱导，然后是特异性适应性免疫，对流感病毒感染提供广泛的保护。
The influenza A non-structural protein 1 (NS1) is known for its ability to hinder the synthesis of type I interferon (IFN) during viral infection. Influenza viruses lacking NS1 (ΔNS1) are under clinical development as live attenuated human influenza virus vaccines and induce potent influenza virus-specific humoral and cellular adaptive immune responses. Attenuation of ΔNS1 influenza viruses is due to their high IFN inducing properties, that limit their replication in vivo. This study demonstrates that pre-treatment with a ΔNS1 virus results in an antiviral state which prevents subsequent replication of homologous and heterologous viruses, preventing disease from virus respiratory pathogens, including SARS-CoV-2. Our studies suggest that ΔNS1 influenza viruses could be used for the prophylaxis of influenza, SARS-CoV-2 and other human respiratory viral infections, and that an influenza virus vaccine based on ΔNS1 live attenuated viruses would confer broad protection against influenza virus infection from the moment of administration, first by non-specific innate immune induction, followed by specific adaptive immunity.
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